'Arsenic life' debate still percolates

Other scientists are analyzing the controversial strain of bacteria that biologist Felisa Wolfe-Simon and her colleagues found in California's Mono Lake.

It's been one year since researchers shook up the scientific world by claiming they bred bacteria that used arsenic in place of phosphorus, and the controversy is still simmering: The lead researcher and her critics say they're taking a closer look at the microbe at the center of the "weird life" claims.

After hitting the highs and the lows of academic acclaim, Felisa Wolfe-Simon has left her original research group and joined up with Lawrence Berkeley National Laboratory in California to continue her research into the bacterium known as GFAJ-1, which gets its name from the acronym for "Give Felisa a Job." (No joke!)

"There is so much work to do we're focusing on that and look forward to communicating our efforts in the coming months," Wolfe-Simon told me in an email this week.

Meanwhile, Wolfe-Simon's highest-profile critic, University of British Columbia microbiologist Rosie Redfield, took on the task of replicating the GFAJ-1 experiment. "I'm doing this even though I agree with all the other researchers who said this result is almost certainly wrong," Redfield told me. "Scientifically, it's really kind of a waste of time to try to replicate this yourself. But there's always the possibility that you could be wrong. And more than that, there was just a general sense that, you know, somebody should try."

Redfield has sent purified DNA samples to collaborators at Princeton University for mass spectrometry analysis — to see whether any arsenic was really taken up into the molecular structure. "We just got the DNA from Rosie Redfield," one of those collaborators, Leonid Kruglyak, told me this week. A graduate student in Kruglyak's lab, Marshall Louis Reaves, is currently working out the protocols for analyzing the DNA.

"We want to be able to fragment the DNA and run the fragments on the mass spectrometer," Krugylak said. "Those fragments should look quite different in the mass spectrometer if there is arsenate."

Just today, another team of researchers, led by Simon Silver of the University of Illinois at Chicago, announced that they have sequenced GFAJ-1's genome and will be analyzing it for new clues in the case.

Argonne National Laboratory's Jack Gilbert, a member of the team, characterized himself as a "100 percent skeptic" about the findings announced a year ago, but said that the gene sequence was still worth having. He and his colleagues have already found some interesting genetic twists, even if there's no evidence of arsenic in the DNA. "It's interesting to have this information to determine what the mechanism might be if other evidence shows this to be true," he explained.

Gilbert said it was mere coincidence that the genome sequence was published online exactly one year after Wolfe-Simon and her colleagues kicked off the controversy. "I hadn't even considered that today was the anniversary," he told me.

Why all the fuss?The case of GFAJ-1 is significant on more than one level.

If the central claim of the original paper holds true, that means the machinery of life can be tinkered with to replace one seemingly essential chemical — phosphorus — with a different chemical that's seemingly inimical to life. One of Wolfe-Simon's original collaborators, Arizona State University astrobiologist Paul Davies, has long maintained that "weird life," built on a different biochemical platform, could exist right under our noses and we wouldn't know it.

The prospect of weird life on Earth would also argue in favor of widening the search for weird life on other worlds, perhaps as close as Mars or the Saturnian moon Titan. That's what led NASA to tout the research a year ago as having extraterrestrial implications. "The definition of life has just expanded," said Ed Weiler, an associate administrator at the space agency. The news reports went even farther. Here's a typical headline: "NASA Discovers Alien Life in California."

Actually, what Wolfe-Simon and her colleagues did was to take an existing strain of salt-loving bacterla from California's Mono Lake, and try to breed it in the presence of high concentrations of arsenic. GFAJ-1 emerged as the best prospect: The research team said it seemed to take hold in the high-arsenic environment, and they said their molecular analysis suggested that arsenic-based compounds known as arsenates were incorporated in the place of phosphates.

The bacteria in the arsenic-rich culture weren't aliens at all. But for many chemists and microbiologists, the research team's claims, published online by the journal Science on Dec. 2, 2010, were as hard to believe as reports of a UFO landing.

One chemist, Steven Benner of the Florida-based Foundation for Applied Molecular Evolution, said he bet Wolfe-Simon $100 that the arsenic wasn't taken up in the DNA. Benner said in an email this week that the proposition was "still in limbo ... so the bet is not yet collected." (Wolfe-Simon told me she doesn't remember the bet.)

The skepticism over the reported results erupted almost immediately in a wave of blog postings and Twitter updates from commentators and scientists, including Redfield. As a result, the #arseniclife case quickly became a case study for instant peer review, mediated by the Internet. It also turned into a case study for open science, in which researchers share their results as they become available rather than holding them back until they're published in a journal.

Redfield emerged as a strong voice, for the skeptics as well as for the open-science movement. Her technical criticisms focused on the way that the bacteria samples were handled. "The way they isolated their DNA was almost 'I can't believe they did this' badly done," she told me this week. Such criticism led Science's editors to hold back the on-paper publication of the research for months, until eight sets of technical comments could be collected from Redfield and other observers and vetted through peer review. Wolfe-Simon and her colleagues were also given space to respond to the technical comments.

"That was pretty unprecedented," said Ginger Pinholster, director of the Office of Public Programs at the American Association for the Advancement of Science, which publishes the journal Science.

The next stepsSince then, the focus has shifted from the headlines to the labs. A Popular Science profile of Wolfe-Simon created a bit of a stir a couple of months ago: She was quoted as saying that she was "basically evicted" from her research group and worried that "it's quite possible that my career is over."

But during this week's email exchange, Wolfe-Simon told me that the "Popular Science article quotes were not what I said," and that "what matters now is what these organisms are telling us about biology, and that is my focus." Here are some reflections on the one-year anniversary from one of her emails to me:

"What a busy year it has been!

"With the generous support of NASA, we are able now to dive deep and explore this scientific discovery. After such a discovery comes the time-intensive process of rigorous testing. We aim to unravel the mechanisms behind how this microbe accomplishes the ability to flourish and grow despite uptake and utilization of arsenic. This systematic rigorous testing is critical and needed to build upon an initial discovery of this type.

"To this end, I have joined the Lawrence Berkeley National Laboratory in collaboration with Dr. John Tainer and his group there. LBNL provides the diverse intellectual and material resources of a major national laboratory, affording us the opportunity to pursue our efforts to test multiple aspects and implications of the work efficiently and stringently. LBNL synergistically complements the generous financial support from NASA.

"Currently, we have made significant headway in optimizing the growth conditions of GFAJ-1 and preparing samples for a wide range of analyses, including biomolecule crystallization and metabolite characterization. There is so much work to do we're focusing on that and look forward to communicating our efforts in the coming months. ...

"I maintain my serious commitment to science and the process of data-driven research. I look forward to speaking with you some time in the not too distant future after we make additional scientific progress."

Other researchers are delving into the mysteries of GFAJ-1 as well, even though they don't think the claims about arseno-DNA and other "weird life" wonders will hold up. "I don't have any money for this," Redfield told me. "This is just a side project in what would be my spare time, if professors have any spare time."

Redfield says the projects she gets paid for are more likely to be scientifically productive, but they're not as interesting to the general public. "This struck me as an opportunity to do science openly in a circumstance where people would be actually interested in what I'm doing, and what the results were," she said.

Now the fruits of her GFAJ-1 labors are in the hands of Kruglyak and his colleagues. If the arsenic in the samples has really been incorporated in the DNA, rather than merely representing sample contamination, traditional genetic sequencing techniques would not work. "They could give all sorts of unpredictable results," Kruglyak said. That's why mass spectrometry has to come into play.

Kruglyak can't predict how long it will take to get the answers. "It always takes longer than whatever I would say," he told me. "I would hope it's weeks, not months."

Meanwhile, Gilbert and his colleagues will continue studying GFAJ-1's genetic makeup. He told me "there's nothing spectacularly amazing" about the bacteria, which was not subjected to the high-arsenic treatment applied by Wolfe-Simon's team and by Redfield. But Gilbert said the raw bacteria's genome has some intriguing twists nevertheless.

"What is quite interesting is that this has very few arsenic resistance genes, i.e., it does not have the typical suite of genes that would make the cell resistant to arsenic in the environment," he told me in an email. Further study of the genome may at last point to an explanation for GFAJ-1's affinity for arsenic — but as of today, one year after the bacteria came onto the world scene, Gilbert can't predict what that explanation might be.

"We will prod and poke at this thing for another year, and see if there's anything more interesting," he said.